Application of Hydrogels in Heart Valve Tissue Engineering

Abstract

With an increasing number of patients requiring valve replacement, there is heightened interest in advancing heart valve tissue engineering (HVTE) to provide solutions to the many limitations of current surgical treatments. A variety of materials have been developed as scaffolds for HVTE including natural polymers, synthetic polymers, and decellularized valvular matrices. Among them, biocompatible hydrogels are generating growing interest. Natural hydrogels, such as collagen and fibrin, generally show good bioactivity, but poor mechanical durability. Synthetic hydrogels, on the other hand, have tunable mechanical properties; however, appropriate cell-matrix interactions are difficult to obtain. Moreover, hydrogels can be used as cell carriers when the cellular component is seeded into the polymer meshes or decellularized valve scaffolds. In this review, we discuss current research strategies for HVTE with an emphasis on hydrogel applications. The physicochemical properties and fabrication methods of these hydrogels, as well as their mechanical properties and bioactivities are described. Performance of some hydrogels including in vitro evaluation using bioreactors and in vivo tests in different animal models are also discussed. For future HVTE, it will be compelling to examine how hydrogels can be constructed from composite materials to replicate mechanical properties and mimic biological functions of the native heart valve.

Impact of modified gelatin on valvular microtissues

“…Gelatin has similar properties to native collagen, such as RGD peptide sequences, which are essential to stimulate cell attachment, cell migration, cell differentiation, and cell growth (Benton et al, ; Tan & Marra, ). However, due to the thermo‐reversible characteristic of gelatin, cross‐linking is needed to enhance the mechanical properties of the 3D construct (Zhang et al, ; Benton et al, ). In this study, chemically gel‐MOD is cross‐linked with UV irradiation in the presence of Irg or VA. Irg has been largely used in tissue engineering and is noncytotoxic in its native state; however, the photogenerated radical form of Irg can decrease cell viability (Rouillard et al, ).…”

Collagen type I and hyaluronic acid based hybrid scaffolds for heart valve tissue engineering

“…Development of a scaffold capable of mimicking the natural heart valve in terms of microstructure, desirable mechanical, and biological properties is challenging . Homogeneous/single‐polymer scaffolds are not able to mimic the heterogeneous microstructure of natural heart valve ECM .…”

“…Development of a scaffold capable of mimicking the natural heart valve in terms of microstructure, desirable mechanical, and biological properties is challenging. [10,11] Homogeneous/single-polymer scaffolds are not able to mimic the heterogeneous microstructure of natural heart valve ECM. [12,13] Therefore, a hybrid scaffold with heterogeneous microstructure taking advantage of its constituent natural polymers has the potential to meet these challenges.…”

Rational Design of a Conductive Collagen Heart Patch

“…Hydrogels, and specifically collagen, are ideal materials for TE matrices due to their versatility of fabrication in various shape, biocompatibility, ability to deliver therapeutic agents, and flexibility . Hydrogels are typically characterised by a relatively low toughness leading to mechanical failure under cardiac beating conditions and poor electronic conductance.…”

“…[9,10] Hydrogels, and specifically collagen, are ideal materials for TE matrices due to their versatility of fabrication in various shape, biocompatibility, ability to deliver therapeutic agents, and flexibility. [11][12][13][14][15] Hydrogels are typically characterised by a relatively low toughness leading to mechanical failure under cardiac beating conditions and poor electronic conductance. As such, mechanically strong and electronically conductive additives such as carbon nanotubes (CNTs) have been proposed for incorporation to dramatically improve the performance of these hydrogels as a TE matrix for MI.…”